This proposal sets out to discover new metal complexes which have significant antineoplastic activity. The choice of metal binding ligands for this study is based on the requirement that they be known active antitumor agents. The principal model compound for this approach will be bleomycin which is isolated from Streptomyces verticillus as a copper complex. The chemical and biochemical mechanism of action of complexes with antitumor activity will be studied. An in vitro system containing Ehrlich ascites cells and a metal-free medium will be used to screen for active metal complexes and to make comparisons of activity and biochemical effects between metal complex and metal-free ligand. Studies on the chemistry of the metal complexes will be used to guide the investigation into modes of interaction of the metal complexes with cells. Spectroscopic and other analytical methods will be used to follow these reactions and consideration of the biochemical effects of the compounds will begin at the level of DNA synthesis.